Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

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Lecarpentier , J , Silvestri , V , Kuchenbaecker , K B , Barrowdale , D , Dennis , J , McGuffog , L , Soucy , P , Leslie , G , Rizzolo , P , Navazio , A S , Valentini , V , Zelli , V , Lee , A , Al Olama , A A , Tyrer , J P , Southey , M , John , E M , Conner , T A , Goldgar , D E , Buys , S S , Janavicius , R , Steele , L , Ding , Y C , Neuhausen , S L , Hansen , T V O , Osorio , A , Weitzel , J N , Toss , A , Medici , V , Cortesi , L , Zanna , I , Palli , D , Radice , P , Manoukian , S , Peissel , B , Azzollini , J , Viel , A , Cini , G , Damante , G , Tommasi , S , Peterlongo , P , Fostira , F , Hamann , U , Evans , D G , Henderson , A , Brewer , C , Kiiski , J I , Aittomäki , K , Khan , S , Nevanlinna , H , EMBRACE , GEMO Study Collaborators , HEBON & KConFab Investigators 2017 , ' Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores ' , Journal of Clinical Oncology , vol. 35 , no. 20 , pp. 2240-+ . https://doi.org/10.1200/JCO.2016.69.4935

Title: Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores
Author: Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Al Olama, Ali Amin; Tyrer, Jonathan P.; Southey, Melissa; John, Esther M.; Conner, Thomas A.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V. O.; Osorio, Ana; Weitzel, Jeffrey N.; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D. Gareth; Henderson, Alex; Brewer, Carole; Kiiski, Johanna I.; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; EMBRACE; GEMO Study Collaborators; HEBON; KConFab Investigators
Contributor: University of Helsinki, Clinicum
University of Helsinki, Kristiina Aittomäki / Principal Investigator
University of Helsinki, Department of Obstetrics and Gynecology
University of Helsinki, HUS Gynecology and Obstetrics
Date: 2017-07-10
Language: eng
Number of pages: 17
Belongs to series: Journal of Clinical Oncology
ISSN: 0732-183X
URI: http://hdl.handle.net/10138/203383
Abstract: PurposeBRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigatedfor the first time to our knowledgeassociations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction.Materials and MethodsWe genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights.ResultsIn male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 x 10(-6)). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 x 10(-9)). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively.ConclusionPRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.
Subject: GENOME-WIDE ASSOCIATION
SUSCEPTIBILITY LOCI
FUNCTIONAL VARIANTS
GENETIC-VARIANTS
IDENTIFICATION
OVERDIAGNOSIS
3122 Cancers
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